Skin rejuvenation cream

ABSTRACT

The subject invention relates to a skin cream that can be used to moisturize and rejuvenate skin that has been damaged by exposure to sunlight or which has simply been affected over the years by intrinsic aging. It inhibits the formation of wrinkles and in some cases reduces the depth of existing wrinkles or eliminates them entirely. This invention is based upon the discovery that alkyl lactates, such as ethyl lactate, can be used to improve the penetration of active ingredients in skin care formulations deep into lower layers of the skin tissue. The present invention more specifically discloses a topical formulation comprising ascorbic acid, an amino acid selected from the group consisting of phenylalanine and tyrosine, a non-toxic zinc salt, an alkyl lactate, and a pharmaceutically acceptable carrier.

This patent application claims benefit of U.S. Provisional PatentApplication Ser. No. 60/877,202, filed on Dec. 26, 2006. The teachingsof U.S. Provisional Patent Application Ser. No. 60/877,202 areincorporated herein by reference in their entirety.

BACKGROUND OF THE INVENTION

Skin care has been practiced for thousands of years, dating back to theAncient Egyptians. Cleopatra was known for her skin car regimen, and issaid to have discovered some of the first anti-aging methods. Skin carehas evolved through the years with every generation being eager to slow,prevent or reverse the aging process.

Countless skin care products are commercially available forbeautification of the skin and to fight wrinkle formation. For example,U.S. Pat. No. 4,938,969 discloses a composition for reducing the depthor intensity of fine wrinkles in skin affected by intrinsic orphoto-induced aging. The topical formulation described by U.S. Pat. No.4,938,969 is comprised of ascorbic acid, tyrosine and a non-toxic zincsalt and is preferably formulated in a hydrophilic ointment or creambase. This composition is reported to be effective for the treatment ofaging or photo-damaged skin and in reducing wrinkles.

The effectiveness of all skin care products is normally contingent upondelivery of the active ingredients therein through the stratum corneumand viable epidermis into the dermis layer of the skin structure. Thisis because the active ingredients in the skin care product cannot beeffective unless they penetrate through the dead layers of skin tissueand into the dermis layer of living skin cells. This is normally adifficult proposition for water soluble active ingredients, such asascorbic acid, because the stratum corneum is a good water barrier. Thestratum corneum and viable epidermis act to protect the body by holdingwater therein to prevent dehydration and by keeping external water whichis frequently contaminated out of the body.

SUMMARY OF THE INVENTION

The subject invention relates to a skin cream that can be used torejuvenate skin that has been damaged by exposure to sunlight or whichhas simply been affected over the years by intrinsic aging. It can alsobe used to slow the rate of photo-induced aging to maintain beautifulskin tone and texture over the years. It inhibits the formation ofwrinkles and in some cases reduces the depth of existing wrinkles oreliminates them entirely. In some cases, the skin cream of thisinvention also lightens age spots and other types of blemishesassociated with aging.

The skin cream of this invention is non-irritating and can be used tosoothe the pain of sunburns and in the treatment of red, irritated, dry,cracked or itchy skin. It can also be used in treating atopicdermatitis, psoriasis, and ichthyosis by moisturizing the skin. The skincream of this invention is typically applied to the face, décolletage,and/or hands of a patient. However, it can be generally used anywhere onthe skin of a patient's body. For instance, it can also be applied tothe patient's feet, chest, back, legs, ankles, arms, and/or wrists asdesired.

This invention is based upon the discovery that alkyl lactates, such asethyl lactate, can be used to improve the penetration of activeingredients in skin care formulations deep into lower layers of the skintissue. For instance, ethyl lactate can be included in aqueous basedskin creams, such as oil in water emulsions, to deliver activeingredients deep into the skin structure. Ethyl lactate is particularlydesirable for utilization in conjunction with skin cream formulationsthat contain water soluble active ingredients, such as ascorbic acid(Vitamin C). This is beneficial because the overall effectiveness ofskin creams that utilize ascorbic acid and/or other water soluble activeingredients is contingent upon delivery of the ascorbic acid through theouter layers of the stratum corneum and viable epidermis and into thedermis layer of the skin structure.

The present invention more specifically discloses a topical formulationcomprising about 1 weight percent to about 20 weight percent ascorbicacid, about 1 weight percent to about 10 weight percent of an amino acidselected from the group consisting of phenylalanine and tyrosine, about0.5 weight percent to about 5 weight percent of a non-toxic zinc salt,about 0.01 weight percent to about 20 weight percent of an alkyllactate, wherein the alkyl group in the alkyl lactate contains from 2 toabout 12 carbon atoms, and a pharmaceutically acceptable carrier.

The subject invention further reveals a topical formulation comprisingabout 1 weight percent to about 20 weight percent ascorbic acid, about 1weight percent to about 10 weight percent phenylalanine, about 0.5weight percent to about 5 weight percent of a non-toxic zinc salt, and apharmaceutically acceptable carrier.

The present invention also discloses a method of rejuvenating human skinaffected by intrinsic aging and/or photo-induced aging, said methodcomprising topically applying a topical formulation to the skin, whereinthe topical formulation is comprised of about 1 weight percent to about20 weight percent ascorbic acid, about 1 weight percent to about 10weight percent of an amino acid selected from the group consisting ofphenylalanine and tyrosine, about 0.5 weight percent to about 5 weightpercent of a non-toxic zinc salt, about 0.01 weight percent to about 20weight percent of an alkyl lactate, wherein the alkyl group in the alkyllactate contains from 2 to about 12 carbon atoms, and a pharmaceuticallyacceptable carrier.

The subject invention further discloses a method of rejuvenating humanskin affected by intrinsic aging and/or photo-induced aging, said methodcomprising topically applying a topical formulation to the skin, whereinthe topical formulation is comprised of about 1 weight percent to about20 weight percent ascorbic acid, about 1 weight percent to about 10weight percent phenylalanine, about 0.5 weight percent to about 5 weightpercent of a non-toxic zinc salt, and a pharmaceutically acceptablecarrier.

It is preferred for the alkyl lactate utilized in the topicalformulations of this invention to be ethyl lactate with it being morepreferred for the alkyl lactate to be a mixture of ethyl lactate andiso-amyl lactate. It is also preferred for the topical formulations ofthis invention to contain α-tocopherol, carnosic acid, idebenone, and/orpalmitoyl pentapeptide.

The present invention also reveals a topical formulation comprisingabout 0.01 weight percent to about 5 weight percent idebenone, about0.01 weight percent to about 20 weight percent of an alkyl lactate,wherein the alkyl group in the alkyl lactate contains from 2 to about 12carbon atoms, and a pharmaceutically acceptable carrier.

The subject invention further discloses a topical formulation comprising(1) about 0.01 weight percent to about 2 weight percent of at least onepolyphenolic antioxidant selected from the group consisting of condensedproanthocyanidins, chlorogenic acid, quinic acid, and ferulic acid, (2)about 0.01 weight percent to about 20 weight percent of an alkyllactate, wherein the alkyl group in the alkyl lactate contains from 2 toabout 12 carbon atoms, and (3) a pharmaceutically acceptable carrier.

The present invention also reveals a topical formulation comprisingabout 0.01 weight percent to about 5 weight percent carnosic acid, about0.01 weight percent to about 20 weight percent of an alkyl lactate,wherein the alkyl group in the alkyl lactate contains from 2 to about 12carbon atoms, and a pharmaceutically acceptable carrier.

DETAILED DESCRIPTION OF THE INVENTION

The topical skin cream formulations of this invention will normallycontain from about 1 weight percent to about 20 weight percent ascorbicacid (Vitamin C). Higher levels of ascorbic acid can be used, but do notgenerally yield a better result. However, in cases where the ascorbicacid is utilized at levels of less than about 1 weight percent theimprovement of treated skin in minimal. It is typically preferred forthe ascorbic acid to be utilized in the topical skin cream formulationat a level which is within the range of about 5 weight percent to about15 weight percent. It is typically more preferred for the ascorbic acidto be utilized in the topical skin cream formulation at a level which iswithin the range of about 8 weight percent to about 12 weight percent.For improved long term shelf stability the level of ascorbic acid willtypically be limited to an amount which is within the range of 2 weightpercent to 5 weight percent and preferably within the range of 3 weightpercent to 4.5 weight percent.

The topical skin cream formulations of this invention will alsotypically contain from about 0.1 weight percent to about 5 weightpercent of a non-toxic zinc salt. The skin cream formulation willpreferably contain from about 0.5 weight percent to about 4 weightpercent of the zinc salt and will most preferably contain from about 1to about 3 weight percent of the zinc salt. The zinc salt willpreferably be a water soluble zinc salt, such as zinc bacitracin(baciferm), zinc salicylate (zinc salt of 2-hydroxybenzoic acid), orzinc sulfate. Zinc sulfate is generally preferred for used as the zincsalt. However, zinc salicylate offers the advantage of providingantiseptic action which can be desirable for preventing the growth ofbacteria in the skin cream formulation during storage and can also bebeneficial in certain patients, such as patients suffering from acne.

The topical skin cream formulations of this invention will alsotypically contain from about 1 weight percent to about 10 weight percentof an amino acid selected from the group consisting of phenylalanine andtyrosine. It is normally preferred for the amino acid to bephenylalanine. The skin cream will generally contain from about 2 weightpercent to about 8 weight percent of the amino acid and will preferablycontain from about 2.5 weight percent to about 4 weight percent of theamino acid.

It is important for the topical skin cream formulations of thisinvention to contain an alkyl lactate for the active ingredients,particularly the ascorbic acid, to better penetrate through the stratumcorneum and the viable epidermis to gain entry into the dermis. This isbecause the active ingredients of the skin cream can only serve theirintended purpose after reaching the living dermis layer of the skin. Thealkyl lactate will normally be present in the skin cream formulation ata level which is within the range of about 0.01 weight percent to about20 weight percent. The alkyl lactate will more typically be present inthe skin cream formulation at a level which is within the range of about0.1 weight percent to about 15 weight percent. The alkyl lactate willpreferably be present in the skin cream formulation at a level which iswithin the range of about 0.2 weight percent to about 1 weight percentand will more preferably be present at a level which is within the rangeof about 0.2 weight percent to about 0.5 weight percent.

The alkyl lactate utilized will typically have an alkyl group thatcontains from 2 to about 12 carbon atoms and will accordingly be of thestructural formula:

wherein R represents an straight chained or a branched alkyl group thatcontains from 2 to 12 carbon atoms. It is preferred for the alkyl groupto contain from 2 to about 6 carbon atoms. Ethyl lactate is highlypreferred because it is highly dispersible in aqueous solutions. Ethyllactate is of the structural formula:

and is a colorless liquid having a strong odor. It is preferred toutilize a mixture of ethyl lactate with a higher molecular weight alkyllactate in cases where oil soluble active ingredients, such asα-tocopherol are included in the topical skin cream formulation. Isoamyllactate is preferred for utilization in such mixtures. Isoamyl lactateis of the structural formula:

and is a colorless liquid having a pleasant mild odor.

In cases where a mixture of ethyl lactate and isoamyl lactate areutilized in the skin cream formulation the weight ratio of ethyl lactateto isoamyl lactate will typically be within the range of about 1:10 toabout 20:1. The weight ratio of ethyl lactate to isoamyl lactate willmore typically be within the range of about 1:5 to about 10:1. Suchmixtures of ethyl lactate and isoamyl lactate will preferably containfrom about 30 weight percent to 70 weight percent ethyl lactate and fromabout 30 weight percent to about 70 weight percent isoamyl lactate. Suchmixtures of ethyl lactate and isoamyl lactate will more preferablycontain from about 40 weight percent to 60 weight percent ethyl lactateand from about 40 weight percent to about 60 weight percent isoamyllactate. Such mixtures of ethyl lactate and isoamyl lactate will mostpreferably contain from about 45 weight percent to 55 weight percentethyl lactate and from about 45 weight percent to about 55 weightpercent isoamyl lactate.

It is highly desirable for the skin cream formulations of this inventionto contain α-tocopherol (Vitamin E) for a number of important reasons.For instance, α-tocopherol is a powerful antioxidant that can serve toprotect the skin cells of a patient being treated from photo-induceddamage as well as other causes of oxidative aging. The α-tocopherol alsohelps to preserve the skin cream composition from oxidation duringstorage. This is particularly important in compositions that containhigh levels of ascorbic acid, such as compositions that contain over 3weight percent and particularly 5 weight percent ascorbic acid. It wasalso unexpectedly found that α-tocopherol helps to mask the odor ofethyl lactate in the skin cream compositions of this invention. Thismakes the skin cream much more pleasant for patients to use and is ofparticular importance in cases where the patient will used the skincream formulation over a prolonged period of time.

It was found that α-tocopherol helps to prevent the skin creamcompositions of this invention from yellowing due to oxidation of theascorbic acid therein. However, it was unexpectedly found that theα-tocopherol must be present at a specific level to protect ascorbicacid from oxidation and to accordingly prevent the skin creamformulation from yellowing. More specifically, in cases whereα-tocopherol is present at levels of less than about 5 weight percentthe skin cream is prone of yellowing and in cases where the α-tocopherolis present at levels of greater than about 25 weight percent the skincream is also prone to yellowing. In such cases, additionalantioxidants, such as butylated hydroxytoluene (BHT) should be includedin the formulation to prevent oxidation of the ascorbic acid. However,in cases where the α-tocopherol is present at a level which is withinthe range of about 10 weight percent to about 20 weight percent the skincream formulations of this invention the ascorbic acid is resistant ofoxidative degradation. For this reason, it is preferred to includeα-tocopherol at a level which is within the range of about 5 weightpercent to about 25 weight percent with it being more preferred toinclude the α-tocopherol at a level which is within the range of about10 weight percent to about 20 weight percent. In cases where otheragents are used to protect the ascorbic acid from oxidation,α-tocopherol can be beneficially employed in the skin cream at levelswhich are within the range of 1 weight percent to 30 weight percent. Insuch cases the α-tocopherol will typically be employed in the skin creamat levels which are within the range of 2 weight percent to 8 weightpercent and preferably within the range of 3 weight percent to 5 weightpercent. In such formulations it is frequently desirable to includeabout 0.1 weight percent to about 5 weight percent BHT to furtherinhibit yellowing. Such formulations will typically contain from about0.5 weight percent to 2 weight percent BHT and will more typicallycontain from 0.8 weight percent to 1.2 weight percent BHT.

Camosic acid can be included in the skin cream formulations of thisinvention to provide a higher level of protection against photo-inducedand other types of oxidative attack on skin cells. The carnosic acidwill typically be included in the skin cream formulation at a levelwhich is within the range of 0.01 weight percent to 1.5 weight percent.It is normally preferred to include the carnosic acid at a level whichis within the range of 0.05 weight percent to 1 weight percent withlevels of 0.1 weight percent to 0.8 weight percent being most preferred.The carnosic acid is naturally found in Libiatae plants, such asrosemary, marjoram, and sage.

U.S. Pat. No. 5,859,293 and U.S. Pat. No. 5,256,700 disclose techniquesfor extracting high purity carnosic acid from rosemary and sage. Forexample, U.S. Pat. No. 5,256,700 discloses a process for obtainingcarnosic acid comprising extracting a vegetable material selected fromthe group consisting of sage and rosemary with an apolar solvent toobtain an extract containing apolar compounds including carnosic acid,contacting the extract with an adsorbent material having an affinity forpolar compounds for adsorbing the carnosic acid to separate the carnosicacid from the apolar compounds of the extract, desorbing the adsorbentmaterial with a polar solvent to obtain the carnosic acid in the solventand then evaporating the polar solvent from the carnosic acid to obtaina residue containing the carnosic acid.

Mixtures of ethyl lactate and isoamyl lactate can beneficially be usedto extract carnosic acid from Libiatae plants, such as rosemary,marjoram, and sage. For instance, a mixture containing from about 30weight percent to 70 weight percent ethyl lactate and about 30 weightpercent to about 70 weight percent isoamyl lactate can be used toextract carnosic acid from such Libiatae plants. In such a procedure,the mixture of ethyl lactate and isoamyl lactate is mixed with about 30parts by weight to about 70 parts by weight of water and heated to atemperature which is within the range of about 70° C. to about 100° C.Then ground leaves of the Libiatae plant are mixed into the solution ofthe ethyl lactate, isoamyl lactate and water. Then the extract of theLibiatae plant is recovered by filtering it from the solid matter, suchas leaves and plant material. At this point, the extract from theLibiatae plant can be employed in making the skin creams of thisinvention. It should be noted that additional ethyl lactate and/orisoamyl lactate can be added at attain the desired levels in the finalskin cream.

Some methods for the preparation of carnosic acid by chemical synthesishave also been proposed in the literature by W. L. Meyer et al.[Tetrahedron Letters 1966, 4261; 1968, 2963; J. Org. Chem. 41, 1005(1976)]. However, the syntheses involved are long and complex and, foreconomic reasons, cannot be applied to an industrial process. Inaddition, these syntheses lead to racemic mixtures of carnosic acidprecursors and not to the pure enantiomers. It should also be pointedout that these works stop at the preparation of carnosic acid precursorsand omit to describe the final preparation step(s). Another method ofobtaining carnosic acid has been described in the literature byBrieskorn and Domling [Arch. Pharm. 302, 641 (1969)], comprising thecatalytic reduction of carnosol. Once again, the application of thisprocess on a large scale is not be envisaged because carnosol is notreadily available on a commercial basis. For these reasons the carnosicacid used in the skin creams formulations of this invention willnormally be obtained by extraction from a Libiatae plant, such asrosemary or marjoram. Accordingly, rosemary or marjoram extract willtypically be used in the practice of this invention as the source ofcarnosic acid. However, to reduce the possibility of allergic reactionsto the skin cream formulation the skin cream formulation will preferablybe free of rosemary, sage, marjoram and other Libiatae plants.

It is preferred for the skin cream formulations of this invention toalso contain idebenone. The idebenone will typically be present in theskin cream formulation at a level which is within the range of about0.01 weight percent to about 5 weight percent. The idebenone willpreferably be present in the skin cream formulation at a level which iswithin the range of about 0.05 weight percent to about 3 weight percentand will more preferably be present at a level which is within the rangeof about 0.1 weight percent to about 1 weight percent.

Palmitoyl pentapeptide can also be included in the skin creamformulations of this invention. Palmitoyl pentapeptide stimulates humanfibroblasts to produce collagen and elastin which fight wrinkleformation and can reduce or eliminate existing wrinkles. However, aswith all active ingredients in antiwrinkle creams palmitoyl pentapeptideneeds to be delivered deep into the dermis of the skin structure toattain a maximum level of effectiveness. The topical skin creamformulations of this invention accordingly can be used to facilitate thedelivery of the palmitoyl pentapeptide deep into the dermis of apatient. The palmitoyl pentapeptide will normally be included at a levelwhich is within the range of about 0.05 weight percent to about 8 weightpercent. The palmitoyl pentapeptide will more typically be included at alevel which is within the range of about 0.5 weight percent to about 6weight percent, and will preferably be include at a level which iswithin the range of about 1 weight percent to about 5 weight percent.The palmitoyl pentapeptide will more preferably be included at a levelwhich is within the range of 2 weight percent to 4 weight percent.

It can be desirable to include other naturally occurring antioxidants inthe skin cream compositions of this invention. For instance, the extractof the subripe berry of the plant Coffea arabica, from which the ripenedand roasted coffee bean is also derived, can beneficially be utilized inthe skin cream compositions of this invention. This extract is rich innatural polyphenolic antioxidants including condensed proanthocyanidinsand chlorogenic, quinic, and ferulic acids. These polyphenolicantioxidants can be used in the skin cream individually or in variouscombinations to protect skin from free radical oxidative attack.

Skin cream formulations that are comprised of extracts of subripeberries of Coffea Arabica plants, at least one alkyl lactate, and a basecream can also be made in accordance with this invention. Such skincream formulations will typically contain (1) a polyphenolic antioxidantselected from the group consisting of condensed proanthocyanidins,chlorogenic acid, quinic acid, and ferulic acid; (2) at least one analkyl lactate, and (3) a base cream (a pharmaceutically acceptablecarrier). It is typically preferred for a combination of ethyl lactateand isoamyl lactate to be used in such compositions. The total level ofpolyphenolic antioxidants present in such skin cream formulations willtypically be within the range of 0.01 weight percent to 2 weightpercent, based upon the total weight of the skin cream formulation. Skincream formulations of this type will more typically contain from about0.05 weight percent to about 1 weight percent polyphenolic antioxidants,based upon the total weight of the skin cream formulation.

In making the skin cream formulations of this invention the ascorbicacid, the zinc salt, the amino acid, the optional carnosic acid, theoptional palmitoyl pentapeptide, the optional idebenone, and additionaldesired materials are mixed into a pharmaceutically acceptable carrier,such as a base cream. Pharmaceutically acceptable carriers are describedin U.S. Pat. No. 7,022,317 and can be in any presentation form normallyused in cosmetics or dermatology, and it may especially be in the formof an optionally gelled aqueous solution, a dispersion of the lotiontype, optionally a two-phase lotion, an emulsion obtained by dispersinga fatty phase in an aqueous phase (oil/water emulsion) or conversely(water/oil emulsion), or a triple emulsion (water/oil/water oroil/water/oil emulsion) or a vesicular dispersion of ionic and/ornonionic type. These compositions are prepared according to usualmethods. A composition in the form of an oil-in-water emulsion ispreferably used according to this invention.

This composition may be more or less fluid and may have the appearanceof a white or colored cream, an ointment, a milk, a lotion, a serum, apaste or a mousse. It may optionally be applied in the form of anaerosol. It may also be in solid form, in particular in the form of astick. It may be used as a care product, and/or as a makeup product forthe skin.

In a known manner, the composition used according to the invention mayalso contain adjuvants that are common in cosmetics, such as hydrophilicor lipophilic gelling agents, hydrophilic or lipophilic active agents,preserving agents, antioxidants, solvents, fragrances, fillers,UV-screening agents, pigments, odor absorbers and dyestuffs. The amountsof these various adjuvants are those conventionally used in the fieldunder consideration, and, for example, from 0.01% to 20% relative to thetotal weight of the composition. Depending on their nature, theseadjuvants may be introduced into the fatty phase, into the aqueousphase, or into lipid vesicles.

When the composition used according to the invention is an emulsion, theproportion of the fatty phase may range from 5% to 80% by weight andpreferably from 5% to 50% by weight relative to the total weight of thecomposition. The oils, emulsifiers and co-emulsifiers used in thecomposition in emulsion form are chosen from those conventionally usedin the field under consideration. The emulsifier and co-emulsifier arepresent in the composition in a proportion ranging from 0.3% to 30% byweight and preferably from 0.5% to 20% by weight relative to the totalweight of the composition.

As oils that may be used in the invention, mention may be made ofmineral oils (liquid petroleum jelly), oils of plant origin (avocado oilor soybean oil), oils of animal origin (lanolin), synthetic oils(perhydrosqualene), silicone oils (cyclomethicone) and fluoro oils(perfluoropolyethers). Fatty alcohols (cetyl alcohol), fatty acids andwaxes (carnauba wax or ozokerite) may also be used as fatty substances.

As examples of emulsifiers and co-emulsifiers that may be used in theinvention, mention may be made of fatty acid esters of polyethyleneglycol such as PEG-100 stearate, and fatty acid esters of glycerol suchas glyceryl stearate, or mixtures thereof.

Hydrophilic gelling agents that may be mentioned in particular includecarboxyvinyl polymers (carbomer), acrylic copolymers such asacrylate/alkylacrylate copolymers, polyacrylamides, polysaccharides,natural gums and clays, and lipophilic gelling agents that may bementioned include modified clays, for instance bentones, metal salts offatty acids, hydrophobic silica and polyethylenes.

Dermabase cream, Unibase cream, and Vanicream are representativeexamples of commercially available base creams that can be used as thepharmaceutically acceptable carrier in the practice of this invention.

The topical formulations of this invention can also contain: (1)moisturizers, (2) depigmenting or propigmenting agents, (3)antimicrobial agents, (4) anti-pollution agents or free-radicalscavengers, (5) NO-synthase inhibitors, (6) agents for stimulating thesynthesis of dermal or epidermal macromolecules and/or for preventingtheir degradation, (7) agents for stimulating the proliferation offibroblasts or keratinocytes and/or keratinocyte differentiation, (8)dermo-decontracting agents, (9) tensioning agents, (10) calmatives, (11)agents acting on the capillary circulation, and (12) agents acting onthe energy metabolism of cells. Examples of these additional materialsthat can be included in the skin cream formulations of this inventioninclude:

1. Moisturizers

The moisturizers that can be used in the skin cream formulations of thisinvention either act on the barrier function of the skin or as anocclusive compound. Mention may be made of ceramides, sphingoid-basedcompounds, lecithins, glycosphingolipids, phospholipids, cholesterol andits derivatives, phytosterols (stigmasterol, β-sitosterol orcampesterol), essential fatty acids, 1,2-diacylglycerol, 4-chromanone,pentacyclic triterpenes such as ursolic acid, petroleum jelly andlanolin; or a compound that directly increases the water content of thestratum corneum, such as threalose and its derivatives, hyaluronic acidand its derivatives, glycerol, pentanediol, sodium pidolate, serine,xylitol, sodium lactate, polyglyceryl acrylate, ectoin and itsderivatives, chitosan, oligosaccharides and polysaccharides, cycliccarbonates, N-lauroylpyrrolidonecarboxylic acid andN-α-benzoyl-L-arginine; or a compound that activates the sebaceousglands, such as steroid derivatives (such as DHEA, its 7-oxide and17-alkyl derivatives and sapogenins) and vitamin D and its derivatives.These compounds may represent from 0.001% to 30% and preferably from0.01% to 20% relative to the total weight of the composition accordingto the invention. The composition according to the present inventioncomprising the moisturizers mentioned above is advantageously intendedfor preventing or treating dryness of the skin and especially xerosis.

2. Depigmenting or Propigmenting Agent

The depigmenting agents that may be incorporated into the compositionaccording to the present invention comprise, for example, the followingcompounds: kojic acid; ellagic acid; arbutin and its derivatives such asthose described in patent applications EP-895 779 and EP-524 109;hydroquinone; aminophenol derivatives such as those described in patentapplications WO 99/10318 and WO 99/32077, and in particularN-cholesteryloxycarbonyl-para-aminophenol andN-ethyloxycarbonyl-para-aminophenol; iminophenol derivatives, inparticular those described in patent application WO 99/22707;L-2-oxothiazolidine-4-carboxylic acid or procysteine, and also its saltsand esters; ascorbic acid and its derivatives, especially ascorbylglucoside; and plant extracts, in particular extracts of liquorice, ofmulberry and of skullcap, without this list being limiting.

Propigmenting agents that may be mentioned include the extract of burnet(Sanguisorba officinalis) sold by the company Maruzen, and extracts ofchrysanthemum (Chrysanthemum morifolium). The composition according tothe present invention comprising the depigmenting agents mentioned aboveis advantageously intended for preventing or treating hyperpigmentation,in particular pigmentation marks associated with ageing of the skin. Forits part, the composition containing the propigmenting agents mentionedabove is preferably intended for treating baldness.

3. Antimicrobial Agents

The antimicrobial agents that may be used in the composition accordingto the invention may be chosen especially from2,4,4′-trichloro-2′-hydroxydiphenyl ether (or triclosan),3,4,4′-trichlorobanilide, phenoxyethanol, phenoxypropanol,phenoxyisopropanol, hexamidine isethionate, metronidazole and its salts,miconazole and its salts, itraconazole, terconazole, econazole,ketoconazole, saperconazole, fluconazole, clotrimazole, butoconazole,oxiconazole, sulfaconazole, sulconazole, terbinafine, ciclopirox,ciclopiroxolamine, undecylenic acid and its salts, benzoyl peroxide,3-hydroxybenzoic acid, 4-hydroxybenzoic acid, phytic acid,N-acetyl-L-cysteine acid, lipoic acid, azelaic acid and its salts,arachidonic acid, resorcinol, 2,4,4′-trichloro-2′-hydroxydiphenyl ether,3,4,4′-trichlorocarbanilide, octopirox, octoxyglycerine,octanoylglycine, caprylyl glycol, 10-hydroxy-2-decanoic acid,dichlorophenyl imidazole dioxolane and its derivatives, described inpatent WO 93/18743, farnesol and phytosphingosines, and mixturesthereof. The preferred antibacterial agents are triclosan,phenoxyethanol, octoxyglycerine, octanoylglycine, 10-hydroxy-2-decanoicacid, caprylyl glycol, farnesol and azelaic acid. By way of example, theantimicrobial agent may be used in the composition according to theinvention in an amount representing from 0.1% to 20% and preferably from0.1% to 10% relative to the total weight of the composition. Thecomposition containing the antimicrobial agent is particularly suitablefor use in treating acne-prone greasy skin, acne or scalp dandruff.

4. Anti-Pollution Agent or Free-Radical Scavenger

The term “anti-pollution agent” means any compound capable of trappingozone, monocyclic or polycyclic aromatic compounds such as benzopyreneand/or heavy metals such as cobalt, mercury, cadmium and/or nickel. Theterm “free-radical scavenger” means any compound capable of trappingfree radicals. As ozone-trapping agents that may be used in thecomposition according to the invention, mention may be made inparticular of vitamin C and its derivatives including ascorbylglucoside; phenols and polyphenols, in particular tannins, ellagic acidand tannic acid; epigallocatechin and natural extracts containing it;extracts of olive tree leaf; extracts of tea, in particular of greentea; anthocyans; extracts of rosemary; phenol acids, in particularchlorogenic acid; stilbenes, in particular resveratrol;sulphur-containing amino acid derivatives, in particularS-carboxymethylcysteine; ergothioneine; N-acetylcysteine; chelatingagents, for instance N,N′-bis(3,4,5-trimethoxybenzyl)ethylenediamine orone of its salts, metal complexes or esters; carotenoids such ascrocetin; and various starting materials, for instance the mixture ofarginine, histidine ribonucleate, mannitol, adenosine triphosphate,pyridoxine, phenylalanine, tyrosine and hydrolysed RNA, sold by theLaboratoires Serobiologiques under the trade name CPP LS 2633-12F®, thewater-soluble fraction of corn sold by the company Solabia under thetrade name Phytovityl®, the mixture of extract of fumitory and ofextract of lemon sold under the name Unicotrozon C-49® by the companyInduchem, and the mixture of extracts of ginseng, of apple, of peach, ofwheat and of barley, sold by the company Provital under the trade namePronalen Bioprotect®.

As agents for trapping monocyclic or polycyclic aromatic compounds,which may be used in the composition according to the invention, mentionmay be made in particular of tannins such as ellagic acid; indolederivatives, in particular 3-indolecarbinol; extracts of tea, inparticular of green tea, extracts of water hyacinth or Eichhorniacrassipes; and the water-soluble fraction of corn sold by the companySolabia under the trade name Phytovityl®.

Finally, as heavy-metal-trapping agents that may be used in thecomposition according to the invention, mention may be made inparticular of chelating agents such as EDTA, the pentasodium salt ofethylenediaminetetra-methylenephosphonic acid, andN,N′-bis(3,4,5-trimethoxybenzyl)ethylenediamine or one of the salts,metal complexes or esters thereof; phytic acid; chitosan derivatives;extracts of tea, in particular of green tea; tannins such as ellagicacid; sulphur-containing amino acids such as cysteine; extracts of waterhyacinth (Eichhornia crassipes); and the water-soluble fraction of cornsold by the company Solabia under the trade name Phytovityl®.

The free-radical scavengers that may be used in the compositionaccording to the invention comprise, besides certain anti-pollutionagents mentioned above, vitamin E and its derivatives such as tocopherylacetate; bioflavonoids; coenzyme Q10 or ubiquinone; certain enzymes, forinstance catalase, superoxide dismutase, lactoperoxidase, glutathioneperoxidase and quinone reductases; glutathione; benzylidenecamphor;benzylcyclanones; substituted naphthalenones; pidolates; phytanetriol;gamma-oryzanol; lignans; and melatonin.

5. NO-Synthase Inhibitor

Examples of NO-synthase inhibitors that are suitable for use in thepresent invention especially comprise an extract of a plant of thespecies Vitis vinifera which is sold especially by the company Euromedunder the name Leucocyanidines de raisins extra, or by the companyIndena under the name Leucoselect®, or finally by the company Hansenunder the name Extrait de marc de raisin; an extract of a plant of thespecies Olea europaea which is preferably obtained from olive treeleaves and is sold especially by the company Vinyals in the form of adry extract, or by the company Biologia & Technologia under the tradename Eurol BT; and an extract of a plant of the species Gingko bilobawhich is preferably a dry aqueous extract of this plant sold by thecompany Beaufour under the trade name Gingko biloba extrait standard.The composition according to the invention comprising an NO-synthaneinhibitor as defined above can advantageously be used to present ortreat signs of ageing of the skin and/or sensitive skin.

6. Agent for Stimulating the Synthesis of Dermal or EpidermalMacromolecules and/or for Preventing their Degradation

Among the active agents for stimulating dermal macromolecules or forpreventing their degradation, mention may be made of those that act:either on collagen synthesis, such as extracts of Centella asiatica;asiaticosides and derivatives; ascorbic acid or vitamin C and itsderivatives; synthetic peptides such as lamin, biopeptide CL or thepalmitoyloligopeptide sold by the company Sederma; peptides extractedfrom plants, such as the soybean hydrolysate sold by the companyColetica under the trade name Phytokine®; and plant hormones such asauxins and lignans; or on elastin synthesis, such as the extract ofSaccharomyces cerivisiae sold by the company LSN under the trade nameCytovitin®; and the extract of the alga Macrocystis pyrifera sold by thecompany Secma under the trade name Kelpadelie®; or on glycosaminoglycansynthesis, such as the product of fermentation of milk withLactobacillus vulgaris, sold by the company Brooks under the trade nameBiomin Yogourth®; the extract of the brown alga Padina pavonica sold bythe company Alban Muller under the trade name HSP3; and the extract ofSaccharomyces cerevisiae available especially from the company Silabunder the trade name Firmalift® or from the company LSN under the tradename Cytovitin®; or on fibronectin synthesis, such as the extract of thezooplankton Salina sold by the company Seporga under the trade nameGP4G®; the yeast extract available especially from the company AlbanMuller under the trade name Drieline®; and the palmitoyl pentapeptidesold by the company Sederma under the trade name Matrixil®; or on theinhibition of metalloproteases (MMPs), such as, more particularly, MMP1, 2, 3 or 9. Mention may be made of: retinoids and derivatives,oligopeptides and lipopeptides, lipoamino acids, the malt extract soldby the company Coletica under the trade name Collalift®; extracts ofblueberry or of rosemary; lycopene; isoflavones, their derivatives orplant extracts containing them, in particular extracts of soybean (sold,for example, by the company Ichimaru Pharcos under the trade nameFlavosterone SB®), of red clover, of flax, of kakkon, or of sage; or onthe inhibition of serine proteases such as leukocyte elastase orcathepsin G. Mention may be made of: the peptide extract of Leguminosaseeds (Pisum sativum) sold by the company LSN under the trade nameParelastyl®; heparinoids; and pseudodipeptides such as{2-[acetyl-(3-trifluoromethylphenyl)amino]-3-methylbutynylamino}aceticacid.

Among the active agents that stimulate epidermal macromolecules, such asfillagrin and keratins, mention may be made especially of the extract oflupin sold by the company Silab under the trade name Structurine®; theextract of beech Fagus sylvatica buds sold by the company Gattefosseunder the trade name Gatuline®; and the extract of the zooplanktonSalina sold by the company Seporga under the trade name GP4G®.

The composition according to the invention containing one or more of theabove compounds is particularly suitable for use in preventing ortreating signs of ageing of the skin, in particular of loss of firmnessand/or of elasticity of the skin.

7. Agent for Stimulating the Proliferation of Fibroblasts orKeratinocytes and/or Keratinocyte Differentiation

The agents for stimulating the proliferation of fibroblasts that may beused in the composition according to the invention may be chosen, forexample, from plant proteins or polypeptides, extracts, especially ofsoybean (for example an extract of soybean sold by the company LSN underthe name Eleseryl SH-VEG 8 or sold by the company Silab under the tradename Raffermine®); and plant hormones such as gibelrellins andcytokinins.

The agents for stimulating the proliferation of keratinocytes that maybe used in the composition according to the invention especiallycomprise retinoids such as retinol and its esters, including retinylpalmitate; phloroglucinol; extracts of nut cakes sold by the companyGattefosse; and extracts of Solanum tuberosum sold by the companySederma.

The agents for stimulating keratinocyte differentiation comprise, forexample, minerals such as calcium; the extract of lupin sold by thecompany Silab under the trade name Photopreventine®; sodiumbeta-sitosteryl sulphate sold by the company Seporga under the tradename Phytocohesine®; and the extract of corn sold by the company Solabiaunder the trade name Phytovityl®; and lignans such assecoisolariciresinol. The composition according to the inventioncomprising these compounds is preferably intended to be used forpreventing or treating signs of ageing of the skin.

8. Dermo-Decontracting Agent

The dermo-decontracting agents that may be used in the compositionaccording to the invention comprise alverine and its salts, manganesegluconate, Diazepam, the hexapeptide argireline R sold by the companyLipotec, certain carbonylated secondary and tertiary amines, adenosine,and also sapogenins and the natural extracts, in particular of Wild Yam,containing them. The composition according to the invention comprisingthese compounds is preferably intended to be used for preventing ortreating signs of ageing of the skin, and in particular wrinkles.

9. Tensioning Agent

The term “tensioning agent” means a compound capable of exerting tensionon the skin, the effect of which is to temporarily fade outirregularities on the skin's surface, such as wrinkles, and fine lines.Among the tensioning agents that may be used in the compositionaccording to the present invention, mention may be made especially of:(1) synthetic polymers, such as polyurethane latices or acrylic-siliconelatices, in particular those described in patent application EP-1 038519, such as a propylthio(polymethyl acrylate), propylthio(polymethylmethacrylate) and propylthio(polymethacrylic acid) graftedpolydimethylsiloxane, or alternatively a propylthio(polyisobutylmethacrylate) and propylthio(polymethacrylic acid) graftedpolydimethylsiloxane. Such grafted silicone polymers are sold especiallyby the company 3M under the trade names VS 80, VS 70 or LO21 (2)polymers of natural origin, especially (a) polyholosides, for example(i) in the form of starch derived especially from rice, corn, potato,cassaya, pea, Triticum aestivum wheat, oat, etc. or (ii) in the form ofcarrageenans, alginates, agars, gelans, cellulose-based polymers andpectins, advantageously as an aqueous dispersion of gel microparticles,and (b) latices consisting of shellac resin, sandarac gum, dammarresins, elemi gums, copal resins and cellulose-based derivatives, andmixtures thereof, (3) plant proteins and protein hydrolysates, inparticular from corn, rye, Triticum aestivum wheat, buckwheat, sesame,spelt, pea, bean, lentil, soybean and lupin, (4) mixed silicates,especially phyllosilicates and in particular Laponites, (5) waxmicroparticles chosen, for example, from carnauba wax, candelilla waxand alfalfa wax, (6) colloidal particles of mineral filler with anumber-average diameter of between 0.1 and 100 nm and preferably between3 and 30 nm, chosen, for example, fiom: silica, silic-aluminacomposites, cerium oxide, zirconium oxide, alumina, calcium carbonate,barium sulphate, calcium sulphate, zinc oxide and titanium dioxide. Thecompositions according to the invention comprising the above tensioningagents are advantageously intended for treating signs of ageing of theskin, in particular wrinkles and fine lines.

10. Calmatives

As calmatives that may be used in the composition according to theinvention, mention may be made of: pentacyclic triterpenes and extractsof plants (e.g.: Glycyrrhiza glabra) containing them, for instance.beta.-glycyrrhetinic acid and salts and/or derivatives thereof(glycyrrhetinic acid monoglucoronide, stearyl glycyrrhetinate or3-stearoyloxyglycyrrhetic acid), ursolic acid and its salts, oleanolicacid and its salts, betulinic acid and its salts, an extract of Paeoniasuffruticosa and/or lactiflora, salicylic acid salts and in particularzinc salicylate, the phycosaccharides from the company Codif, an extractof Laminaria saccharina, canola oil, bisabolol and camomile extracts,allantoin, Sepivital EPC (phosphoric diester of vitamins E and C) fromSEPPIC, omega-3 unsaturated oils such as musk rose oil, blackcurrantoil, ecchium oil, fish oil, plankton extracts, capryloylglycine,Seppicalm VG (sodium palmitoylproline and Nymphea alba) from SEPPIC, anextract of Pygeum, an extract of Boswellia serrata, an extract ofCentipeda cunnighami, an extract of Helianthus annuus, an extract ofLinum usitatissimum, tocotrienols, extracts of Cola nitida, piperonal,an extract of clove, an extract of Epilobium angustifolium, Aloe vera,an extract of Bacopa moniera, phytosterols, cortisone, hydrocortisone,indomethacin and betamethasone.

11. Agents Acting on the Capillary Circulation

The active agents acting on the capillary circulation (vasoprotective orvasodilating agents) may be chosen from flavonoids, ruscogenins,esculosides, escin extracted from common horse chestnut, nicotinates,heperidine methyl chalcone, essential oils of lavender or of rosemary,and extracts of Ammi visnaga. The amount of these active agents may varywithin a wide range. In general, these active agents are present in aconcentration ranging from 0.01% to 15% and preferably from 0.05% to 10%by weight relative to the total weight of the composition.

12. Agents Acting on the Energy Metabolism of Cells

The active agents concerned are those acting on the energy metabolism ofthe skin, for instance, and in a non-limiting manner, ATP synthesis, andalso those involved in the respiratory chain of the cell or in theenergy reserves. Mention may be made of coenzyme Q10 (ubiquinone),cytochrome C, creatine or phosphocreatine.

This invention is illustrated by the following examples that are merelyfor the purpose of illustration and are not to be regarded as limitingthe scope of the invention or the manner in which it can be practiced.Unless specifically indicated otherwise, parts and percentages are givenby weight.

EXAMPLE 1

In this experiment a topical skin cream was made utilizing Vanicream™skin cream as the base cream. Vanicream™ skin cream is a non-greasy,non-comedogenic oil-in-water emulsion that consists of purified water,white petrolatum, cetearyl alcohol and ceteareth-20, sorbitol solution,propylene glycol, simethicone, glyceryl monostearate, polyethyleneglycol monostearate, sorbic acid, and butylated hydroxytoluene (BHT). Inthe procedure used 1 g (gram) of ascorbic acid, 500 mg (milligrams) ofzinc sulfate, 200 mg of idebenone, and 500 mg of phenylalanine weremixed into 10 grams of the Vanicream™ base cream. Then, the liquidcomponents (1.5 g of α-tocopherol, 100 mg of ethyl lactate, and 50 mg ofrosemary extract) were mixed into the formulation.

The topical skin cream formulation made was soothing when applied to dryskin and had good moisturizing characteristics. It also provided a nicewarm glow to skin onto which it was applied. This skin cream formulationhad a slight odor, but was not obnoxious. It did not yellow after beingstored at room temperature for three weeks.

EXAMPLE 2

In this experiment a topical skin cream was made using the proceduredescribed in Example 1 except one drop of mango oil was added to theformulation with the liquid components. The topical skin creamformulation made was soothing when applied to dry skin and had goodmoisturizing characteristics. It also provided a nice warm glow to skinonto which it was applied. This skin cream formulation had a verypleasant mango fragrance. In fact, the odor of the ethyl lactate wascompletely masked. It did not yellow after being stored at roomtemperature for three weeks.

EXAMPLE 3

In this experiment a topical skin cream was made using the proceduredescribed in Example 1 except that α-tocopherol was not included in theformulation. The topical skin cream formulation made was soothing whenapplied to dry skin and had good moisturizing characteristics. This skincream formulation had a strong odor which was deemed to be obnoxious.This skin cream formulation yellowed significantly after being stored atroom temperature for three weeks

EXAMPLE 4

In this experiment a topical skin cream was made using the proceduredescribed in Example 1 except that the level of α-tocopherol was reducedto 500 mg. The topical skin cream formulation made was soothing whenapplied to dry skin and had good moisturizing characteristics. This skincream formulation had a slight odor, but was not obnoxious. However,this skin cream formulation yellowed after being stored at roomtemperature for three weeks

EXAMPLE 5

In this experiment a topical skin cream was made using the proceduredescribed in Example 1 except that the level of α-tocopherol wasincreased to 3 grams. The topical skin cream formulation made wassoothing when applied to dry skin and had good moisturizingcharacteristics. It also provided a nice warm glow to skin onto which itwas applied. This skin cream formulation had a slight odor, but was notobnoxious. However, this skin cream formulation yellowed significantlyafter being stored at room temperature for three weeks

EXAMPLE 6

In this experiment a topical skin cream was made using the proceduredescribed in Example 1 except that 35 mg of isoamyl lactate was added tothe formulation with the liquid components. The topical skin creamformulation made was soothing when applied to dry skin and had goodmoisturizing characteristics. This skin cream formulation had a slightodor, but was not obnoxious.

EXAMPLE 7

In this experiment a topical skin cream was made using the proceduredescribed in Example 6 except that one drop of mango oil was added tothe formulation with the liquid components. The topical skin creamformulation made was soothing when applied to dry skin and had goodmoisturizing characteristics. It also provided a nice warm glow to skinonto which it was applied. This skin cream formulation had a verypleasant mango fragrance. In fact, the odor of the ethyl lactate wascompletely masked.

EXAMPLE 8

In this experiment a topical skin cream was made using the proceduredescribed in Example 1 except that tyrosine was substituted for thephenylalanine. The topical skin cream formulation made was soothing whenapplied to dry skin and had good moisturizing characteristics. It alsoprovided a nice warm glow to skin onto which it was applied. This skincream formulation had a slight odor, but was not obnoxious. It did notyellow after being stored at room temperature for three weeks.

EXAMPLE 9

In this experiment a topical skin cream was made using the proceduredescribed in Example 8 except one drop of mango oil was added to theformulation with the liquid components. The topical skin creamformulation made was soothing when applied to dry skin and had goodmoisturizing characteristics. It also provided a nice warm glow to skinonto which it was applied. This skin cream formulation had a verypleasant mango fragrance. In fact, the odor of the ethyl lactate wascompletely masked. It did not yellow after being stored at roomtemperature for three weeks.

EXAMPLE 10

In this experiment a topical skin cream was made utilizing Vanicream™skin cream as the base cream. In the procedure used 1 g (gram) ofascorbic acid, 500 mg (milligrams) of zinc sulfate, 100 mg of idebenone,and 500 mg of phenylalanine were mixed into 10 grams of the Vanicream™base cream. Then, the liquid components (1.5 g of α-tocopherol, 70 mg ofethyl lactate, 30 mg of isoamyl lactate, 50 mg of rosemary extract, andone drop of mango oil) were mixed into the formulation. The formulationwas mixed with a stirring rod for about 5 minutes to attain a uniformcream composition.

This skin cream formulation made in this experiment had a very pleasantmango fragrance. The odor of the ethyl lactate was completely masked bythe isoamyl lactate and the mango. This skin cream composition wasevaluated as a facial cream by three adult females. These femalesubjects applied this skin cream to their faces in the morning afterwashing their faces. It was reported to have good moisturizingcharacteristics and was further reported to provide the facial skin towhich it was applied with a warm glow. After the skin cream had beenabsorbed into the skin (dried) the subjects applied their makeupfoundation as usual. All of the subjects reported that their foundationglided on more easily than usual. It was further reported that the skincream composition made a good base for their foundation and helped toprevent the foundation from encrusting or caking. The subjects reportedthat their makeup did not dissipate and remained fresh over the courseof the day. Accordingly, the subjects reported that the facial creamcould conveniently be used in conjunction with makeup. None of thesubject found the skin cream of this invention to be irritating and allof the subjects observed a reduction in roughness and dryness of theirfacial skin. All of the subjects further reported an improvement in thetexture, softness, smoothness, tone, clarity, and radiance of their skinwithin 30 minutes of application.

EXAMPLE 11

One of the female subjects repeated the procedure described in Example10, except that she applied MD Forté sunscreen to her face afterallowing the facial cream of this invention to be absorbed into herskin. She again reported that her foundation makeup glided on moreeasily than usual. It was again reported that the skin cream compositionmade a good base for her foundation and helped to prevent it fromencrusting or caking. She found that her makeup did not dissipate andremained fresh over the course of the day. She observed a reduction inroughness and dryness of her facial skin and again reported animprovement in the texture, softness, smoothness, tone, clarity, andradiance of her skin within 30 minutes of the application. Accordingly,she reported that the facial cream could conveniently be used as part ofa daily regimen that includes the application of sunscreen followed bymakeup.

EXAMPLE 12

In this experiment a marjoram extract containing carnosic acid wasprepared. In the procedure used a mixture containing one part by weightethyl lactate, one part by weight isoamyl lactate, and one part byweight distilled water was heated to about 90° C. Then, 4 grams ofground marjoram leaves were mixed into 12 grams of the liquid mixtureand agitated for about 10 minutes. At that point, the mixture wasfiltered through a coffee filter to separate the liquid extract from theremaining solid material, such as leaves and plant matter. The marjoramextract was then used in making skin cream samples in accordance withthis invention.

EXAMPLE 13

In this experiment a topical skin cream was made utilizing the marjoramextract made in Example 12. In the procedure used Vanicream™ skin creamwas again used as the base cream. In the procedure used 1 g (gram) ofascorbic acid, 500 mg (milligrams) of zinc sulfate, 200 mg of idebenone,and 500 mg of phenylalanine were mixed into 10 grams of the Vanicream™base cream. Then, 1.5 g of α-tocopherol and 150 mg of the marjoramextract were mixed into the formulation.

The topical skin cream formulation made was soothing when applied to dryskin and had good moisturizing characteristics. It also provided a nicewarm glow to skin onto which it was applied. This skin cream formulationhad a much more pleasing odor than did the formulation made in Example 1with ethyl lactate and Rosemary extract. It was determined that themarjoram extract made in Example 12 was characterized by a much lessintense odor than was exhibited by the Rosemary extract. In any case theskin cream made did not yellow after being stored at room temperaturefor three weeks.

EXAMPLE 14

In this experiment a topical skin cream was again made utilizing themarjoram extract made in Example 12. In the procedure used Vanicream™skin cream was again used as the base cream. In the procedure used 12 gof ascorbic acid, 6 g of zinc sulfate, 1 g of BHT, and 7.5 g ofphenylalanine were mixed into 300 grams of the Vanicream™ base cream.Then. 15 g of α-tocopherol, 1 g of the marjoram extract, and 1 g ofcucumber melon perfume oil were mixed into the formulation. The skincream made in this experiment did not yellow after being stored at roomtemperature for over four months.

This skin cream formulation was then used to treat a male patientsuffering from chronic dry skin on his hand. This patient was 58 yearsold and had suffered from severe dry skin (xerosis) on the palmar of hishand for many years. In fact, this patient's dry skin was so pronouncedthat it frequently developed painful cracks in the skin (fissures) withbleeding occurring from time to time. Over the years this patient hadtreated his chronic dry skin condition with a wide variety ofmoisturizing agents without success. However, the skin cream made inthis experiment was very effective in reversing the xerosis after it wasapplied topically. In fact, the topical application of the skin cream ofthis invention to this patient's hand eliminated the fissures andbleeding. After a few days of applying the skin cream of this inventionhis skin was reported to have returned to normal.

EXAMPLE 15

In this experiment a topical skin cream was again made utilizing themarjoram extract made in Example 12. In the procedure used Vanicream™skin cream was again used as the base cream. In the procedure used 12 gof ascorbic acid, 6 g of zinc sulfate, 1 g of idebenone, 1 g of BHT, and7.5 g of phenylalanine were mixed into 300 grams of the Vanicream™ basecream. Then, 15 g of α-tocopherol, 1 g of the marjoram extract, and 1 gof honeysuckle perfume oil were mixed into the formulation. The skincream made in this experiment did not yellow after being stored at roomtemperature for over four months. It was also reported to exhibit a verypleasant fragrance.

This skin cream formulation was then used to treat a female patientsuffering from chronic dry skin on her feet. This patient was 79 yearsold and suffered from xerosis on her feet. In fact, this patient's dryskin was so pronounced that it frequently developed painful fissures inthe skin with bleeding occurring from time to time. Over the years thispatient had treated her chronic dry skin condition with a wide varietyof moisturizing agents without complete success. However, the topicalapplication of the skin cream made in this experiment was very effectivewith regard to normalizing this patient's skin. In fact, the topicalapplication of the skin cream of this invention to this patient's feetcompletely eliminated her problem with xerosis of the feet. After a fewdays of applying the skin cream of this invention the skin on her feetwas reported to have returned to normal.

EXAMPLE 16

In this experiment a topical skin cream was again made utilizing themarjoram extract made in Example 12. In the procedure used Vanicream™skin cream was again used as the base cream. In the procedure used 12 gof ascorbic acid, 6 g of zinc sulfate, 1 g of idebenone, 1 g of BHT, and7.5 g of phenylatanine were mixed into 300 grams of the Vanicream™ basecream. Then, 15 g of α-tocopherol, 1 g of the marjoram extract, and 1 gof tangerine perfume oil were mixed into the formulation. The skin creammade in this experiment did not yellow after being stored at roomtemperature for over four months. It was also reported to have apleasant fragrance.

This skin cream formulation was then used to treat a female patientsuffering from xerosis on both of her elbows. The skin on the elbows ofthis patient was cracked, peeling and discolored. This patient was 49years old and had previous treated her asteatotic condition of herelbows with a variety of over-the-counter moisturizing creams. However,the over-the-counter commercial products were not effective inmoisturizing this patient's elbows. However, the topical application ofthe skin cream made in this experiment was very effective with regard tomoisturizing the dry skin on this patient's elbows. In fact, the topicalapplication of the skin cream of this invention to this patient's elbowscompletely eliminated her problem within a few days.

EXAMPLE 17

In this experiment a topical skin cream was again made utilizing themarjoram extract made in Example 12. In the procedure used Vanicream™skin cream was again used as the base cream. In the procedure used 12 gof ascorbic acid, 6 g of zinc sulfate, 1 g of idebenone, 1 g of BHT, and7.5 g of phenylalanine were mixed into 300 grams of the Vanicream™ basecream. Then, 15 g of α-tocopherol, 1 g of the marjoram extract, and 1 gof mango perfume oil were mixed into the formulation. The skin creammade in this experiment did not yellow after being stored at roomtemperature for over four months. It was also reported to have apleasant fragrance.

The facial skin of a 49 year old female patient was evaluated utilizinga Visia Complexion Analysis and Statistical Modeling Engine version1.2.0 made by Canfield Imaging Systems to establish a base line withrespect to spots, pores, wrinkles, and texture. After being evaluated,this patient applied the skin cream made in this experiment to her faceboth in the morning and evening every day. After approximately fourmonths the facial skin of this patient was re-evaluated after using thiscream on a daily basis. This analysis showed a 3% reduction in spots, a29% reduction in pores, a 29% reduction in wrinkles and a 26%improvement in skin texture. This patient was elated with the overallimprovement in the appearance of her skin and was particularly delightedwith the perceived reduction in pore size.

EXAMPLE 18

In this experiment a topical skin cream was again made utilizing themarjoram extract made in Example 12. In the procedure used Vanicream™skin cream was again used as the base cream. In the procedure used 12 gof ascorbic acid, 6 g of zinc sulfate, 1 g of idebenone, 1 g of BHT, and7.5 g of phenylalanine were mixed into 300 grams of the Vanicream™ basecream. Then, 15 g of α-tocopherol, 1 g of the marjoram extract, and 1 gof mango perfume oil were mixed into the formulation. The skin creammade in this experiment did not yellow after being stored at roomtemperature for over four months. It was also reported to have apleasant fragrance.

The facial skin of a 49 year old female patient was evaluated utilizinga Visia Complexion Analysis and Statistical Modeling Engine version1.2.0 made by Canfield Imaging Systems to establish a base line withrespect to spots, pores, wrinkles, and texture. After being evaluated,this patient applied the skin cream made in this experiment to her faceboth in the morning and evening every day. After approximately fourmonths the facial skin of this patient was re-evaluated after using thiscream on a daily basis. This analysis showed a 38% reduction in spots, a58% reduction in pores, a 40% reduction in wrinkles and a 54%improvement in skin texture. This patient was elated with the dramaticimprovement in the appearance of her skin.

While certain representative embodiments and details have been shown forthe purpose of illustrating the subject invention, it will be apparentto those skilled in this art that various changes and modifications canbe made therein without departing from the scope of the subjectinvention.

What is claimed is:
 1. A topical formulation comprising about 1 weightpercent to about 20 weight percent ascorbic acid, about 1 weight percentto about 10 weight percent of phenylalanine, about 0.5 weight percent toabout 5 weight percent of a non-toxic zinc salt, a marjoram extractcontaining carnosic acid, about 1 weight percent to about 30 weightpercent α-tocopherol, and about 0.01 weight percent to about 20 weightpercent of a mixture of ethyl lactate and isoamyl lactate, wherein theweight ratio of ethyl lactate to isoamyl lactate is within the range ofabout 1:10 to about 20:1, and a pharmaceutically acceptable carrier. 2.A topical formulation as specified in claim 1 wherein the mixture ofethyl lactate and isoamyl lactate contains from about 30 weight percentto about 70 weight percent ethyl lactate and from about 30 weightpercent to about 70 weight percent isoamyl lactate.
 3. A topicalformulation as specified in claim 1 wherein the mixture of ethyl lactateand isoamyl lactate contains from about 40 weight percent to about 60weight percent ethyl lactate and from about 40 weight percent to about60 weight percent isoamyl lactate.
 4. A topical formulation as specifiedin claim 1 wherein the α-tocopherol is present at a level which iswithin the range of about 2 weight percent to about 8 weight percent. 5.A topical formulation as specified in claim 1 wherein the α-tocopherolis present at a level which is within the range of about 3 weightpercent to about 5 weight percent.
 6. A topical formulation as specifiedin claim 1 wherein the carnosic acid is present at a level which iswithin the range of about 0.01 weight percent to about 1.5 weightpercent, based upon the total weight of the topical formulation.
 7. Atopical formulation as specified in claim 1 which is further comprisedof palmitoyl pentapeptide.
 8. A topical formulation as specified inclaim 1 wherein the mixture of ethyl lactate and isoamyl lactate ispresent at a level which is within the range of about 0.2 weight percentto about 1 weight percent.
 9. A topical formulation as specified inclaim 1 wherein the mixture of ethyl lactate and isoamyl lactate ispresent at a level which is within the range of about 0.2 weight percentto about 0.5 weight percent.
 10. A topical formulation as specified inclaim 1 wherein the ethyl lactate and the isoamyl lactate are providedto the topical formulation by the marjoram extract which is a liquidsystem that includes water, ethyl lactate, and isoamyl lactate.
 11. Atopical formulation as specified in claim 10 wherein the marjoramextract is made by (1) heating a mixture of marjoram leaves in a mixtureof water, ethyl lactate, and isoamyl lactate at an elevated temperaturewhich is within the range of about 70° C. to about 100° C. to produce amixture of the marjoram extract and solid matter, and (2) recovering themarjoram extract from the mixture by filtering out the solid matter. 12.A topical formulation as specified in claim 1 wherein thepharmaceutically acceptable carrier is an oil-in-water emulsion.
 13. Atopical formulation as specified in claim 12 wherein the oil-in-wateremulsion includes white petrolatum.
 14. A topical formulation asspecified in claim 13 wherein the oil-in-water emulsion is furthercomprised of cetearyl alcohol, sorbitol, propylene glycol, simethicone,glyceryl monostearate, polyethylene glycol monostearate, and sorbicacid.